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Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 24117

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Prof. Dr. Rita Cortesi

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Department of Chemical, Pharmaceutical and Agricultural Sciences (DoCPAS), University of Ferrara, 44121 Ferrara, Italy
Interests: nanomedicine; liposomes and lipid-based nanosystems; vesicles; microparticles; biomaterials; drug delivery
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Special Issue Information

Dear Colleagues,

Modern nanotechnology is a multidisciplinary area that has recently led to an increased interest in nanoscale products. Indeed, at present, nanotechnology has a frequent and profound impact on our lives, both positive and negative. In the last few decades, many studies have demonstrated that nanoparticles, and especially lipid nanoparticles, represent a versatile system that is widely used throughout scientific research in numerous applications belonging to different fields, such as electronic, nutraceutical, veterinary, cosmetic, biotechnological, environmental, biomedical, and pharmaceutical. Particularly, lipid-based nanosystems (i.e., nanostructured lipid carriers, solid lipid nanoparticles, nanoemulsions, liposomes, and cubosomes) are largely used to ameliorate active principle solubility or obtain a controlled or target release creating a modifiable system according to product requirements. Indeed, lipid based nanoparticles are able to solubilize a number of molecules with different physicochemical properties in a biocompatible and biodegradable matrix with well-established safety profiles. Moreover, lipid nanoparticles can significantly contribute, for instance, to the field of green nanosystems due to their natural source.

Starting from these premises and on the basis of the interest found by the researchers in the previous Special Issue on “Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields”, we would like to extend the open forum with a second Special Issue. Our primary focus remains to provide the opportunity to share research and findings related to this topic, in the form of original research or review articles, focusing on multiple issues, such as the production, characterization, structure, and innovative aspects of lipid nanoparticles, possibly presenting new preparation methods, advantages, disadvantages, and new applications. Potential topics also include methods used in the functionalization of lipid nanoparticles. Studies with multidisciplinary inputs that offer new methodologies or insights are particularly welcome.

Prof. Dr. Rita Cortesi
Guest Editor

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Keywords

Nanotechnology
Colloidal carriers
SLN, NLC
Physical characteristics
Formulation stability
Preparation methods
Drug delivery
Nanomedicine
Cosmetics
Green agriculture
Characterization

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Published Papers (8 papers)

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Research

16 pages, 5381 KiB

Open AccessArticle

Synthetic and Nanotechnological Approaches for a Diagnostic Use of Manganese

by Maddalena Sguizzato, Petra Martini, Lorenza Marvelli, Walter Pula, Markus Drechsler, Martina Capozza, Enzo Terreno, Lucia Del Bianco, Federico Spizzo, Rita Cortesi and Alessandra Boschi

Molecules 2022, 27(10), 3124; https://doi.org/10.3390/molecules27103124 - 13 May 2022

Cited by 6 | Viewed by 1903

Abstract

The development of multimodal imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) allows the contemporary obtaining of metabolic and morphological information. To fully exploit the complementarity of the two imaging modalities, the design of probes displaying radioactive and magnetic properties at the same time could be very beneficial. In this regard, transition metals offer appealing options, with manganese representing an ideal candidate. As nanosized imaging probes have demonstrated great value for designing advanced diagnostic/theranostic procedures, this work focuses on the potential of liposomal formulations loaded with a new synthesized paramagnetic Mn(II) chelates. Negatively charged liposomes were produced by thin-layer hydration method and extrusion. The obtained formulations were characterized in terms of size, surface charge, efficiency of encapsulation, stability over time, relaxivity, effective magnetic moment, and in vitro antiproliferative effect on human cells by means of the MTT assay. The negatively charged paramagnetic liposomes were monodisperse, with an average hydrodynamic diameter not exceeding 200 nm, and they displayed good stability and no cytotoxicity. As determined by optical emission spectroscopy, manganese complexes are loaded almost completely on liposomes maintaining their paramagnetic properties. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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21 pages, 5422 KiB

Open AccessArticle

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

by Adel M. Ahmad, Hamdoon A. Mohammed, Tarek M. Faris, Abeer S. Hassan, Hebatallah B. Mohamed, Mahmoud I. El Dosoky and Esam M. Aboubakr

Molecules 2021, 26(24), 7491; https://doi.org/10.3390/molecules26247491 - 10 Dec 2021

Cited by 11 | Viewed by 3169

Abstract

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween^® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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14 pages, 14504 KiB

Open AccessArticle

Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm

by Lara El-Hawari and Heike Bunjes

Molecules 2021, 26(19), 6029; https://doi.org/10.3390/molecules26196029 - 4 Oct 2021

Cited by 5 | Viewed by 2381

Abstract

Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc^™) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc^™ membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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20 pages, 5650 KiB

Open AccessArticle

Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir

by Haniza Hassan, Siti Khadijah Adam, Ekram Alias, Meor Mohd Redzuan Meor Mohd Affandi, Ahmad Fuad Shamsuddin and Rusliza Basir

Molecules 2021, 26(18), 5432; https://doi.org/10.3390/molecules26185432 - 7 Sep 2021

Cited by 41 | Viewed by 3576

Abstract

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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18 pages, 2610 KiB

Open AccessArticle

Design of Nanostructured Lipid Carriers Containing Cymbopogon martinii (Palmarosa) Essential Oil against Aspergillus nomius

by Denise Tiemi Uchida, Gabriella Ferreira Siqueira, Edson Marques dos Reis, Fábio Luis Hegeto, Antonio Medina Neto, Adriano Valim Reis, Marcos Luciano Bruschi, Mônica Villa Nova and Miguel Machinski Júnior

Molecules 2021, 26(16), 4825; https://doi.org/10.3390/molecules26164825 - 10 Aug 2021

Cited by 6 | Viewed by 2976

Abstract

Palmarosa essential oil (PEO) is an alternative to synthetic fungicides to control the contamination by food-deteriorating fungi, such as Aspergillus nomius. Nonetheless, the low long-term stability and volatility hamper its utilization. Thus, this study aimed to develop nanostructured lipid carriers (NLCs) containing PEO to improve its stability and consequently prolong the activity against A. nomius. A mixture design was applied to find the best preparation conditions for antifungal activity. The characterization analyses included size measurements, zeta potential (ζ-potential), entrapment efficiency (EE), and antifungal activity (by inhibition of mycelial growth (IMG) and/or in situ test (pre-contaminated Brazil nuts) tests). The nanocarriers presented particle sizes smaller than 300 nm, homogeneous size distribution, ζ-potential of −25.19 to −41.81 mV, and EE between 73.6 and 100%. The formulations F5 and F10 showed the highest IMG value (98.75%). Based on the regression model, three optimized formulations (OFs) were tested for antifungal activity (IMG and in situ test), which showed 100% of inhibition and prevented the deterioration of Brazil nuts by A. nomius. The preliminary stability test showed the maintenance of antifungal activity and physicochemical characteristics for 90 days. These results suggest a promising system as a biofungicide against A. nomius. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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11 pages, 8029 KiB

Open AccessArticle

Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence

by Carmelo Puglia, Debora Santonocito, Giuseppe Romeo, Sebastiano Intagliata, Giovanni Luca Romano, Enrica Strettoi, Elena Novelli, Carmine Ostacolo, Pietro Campiglia, Eduardo Maria Sommella, Rosario Pignatello and Claudio Bucolo

Molecules 2021, 26(15), 4673; https://doi.org/10.3390/molecules26154673 - 2 Aug 2021

Cited by 20 | Viewed by 2998

Abstract

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3′,6′-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9′-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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14 pages, 3396 KiB

Open AccessArticle

Assessment of the In Vivo Release and Biocompatibility of Novel Vesicles Containing Zinc in Rats

by Liliana Mititelu-Tartau, Maria Bogdan, Daniela Angelica Pricop, Beatrice Rozalina Buca, Ana-Maria Pauna, Lorena Anda Dijmarescu, Ana-Maria Pelin, Liliana Lacramioara Pavel and Gratiela Eliza Popa

Molecules 2021, 26(13), 4101; https://doi.org/10.3390/molecules26134101 - 5 Jul 2021

Cited by 1 | Viewed by 2160

Abstract

This paper is focused on the in vivo release and biocompatibility evaluation in rats of some novel systems entrapping zinc chloride in lipid vesicles. The particles were prepared by zinc chloride immobilization inside lipid vesicles made using phosphatidylcholine, stabilized with 0.5% chitosan solution, and dialyzed for 10 h to achieve a neutral pH. The submicrometric systems were physico-chemically characterized. White Wistar rats, assigned into four groups of six animals each, were treated orally with a single dose, as follows: Group I (control): deionized water 0.3 mL/100 g body weight; Group II (Zn): 2 mg/kg body weight (kbw) zinc chloride; Group III (LV-Zn): 2 mg/kbw zinc chloride in vesicles; Group IV (LVC-Zn): 2 mg/kbw zinc chloride in vesicles stabilized with chitosan. Haematological, biochemical, and immune parameters were assessed after 24 h and 7 days, and then liver fragments were collected for histopathological examination. The use of zinc submicrometric particles—especially those stabilized with chitosan—showed a delayed zinc release in rats. No substantial changes to blood parameters, plasma biochemical tests, serum complement activity, or peripheral neutrophils phagocytic capacity were noted; moreover, the tested substances did not induce liver architectural disturbances. The obtained systems provided a delayed release of zinc, and showed good biocompatibility in rats. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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17 pages, 5280 KiB

Open AccessArticle

Quality by Design for Development, Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery

by Tamer A. Ismail, Tamer M. Shehata, Dalia I. Mohamed, Heba S. Elsewedy and Wafaa E. Soliman

Molecules 2021, 26(11), 3454; https://doi.org/10.3390/molecules26113454 - 7 Jun 2021

Cited by 38 | Viewed by 3589

Abstract

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (3²) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment. Full article

(This article belongs to the Special Issue Preparation, Characterization, and Effect of Lipid Nanoparticles Used in Different Application Fields II)

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